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Bisphosphonate Therapy after Liver Transplant Improves Bone Mineral Density and Reduces Fracture Rates: An Updated Systematic-Review and Meta-Analysis

Owen Tsung Wen Ho 1Winston Cheng Ann Ng 1Zachariah Gene Wing Ow 1Yeung Jek Ho 1Wen Hui Lim 1Jie Ning Yong 1Renaeta Shiqi Wang 1Keng Lin Wong 1 2Cheng Han Ng 1Mark D Muthiah 1 3 4Claire Min-Li Teo 5

Transpl Int. 2021 Apr 21.doi: 10.1111/tri.13887. .


Aim: To investigate the efficacy of bisphosphonates and compare oral and IV formulations on bone mineral density (BMD) and fracture incidence in post-orthotopic liver transplant (OLT) patients.

Methods: Electronic databases were searched, and six RCTs and three cohort studies were included out of 711 articles. Main outcomes included post-OLT BMD changes, fracture incidence, and treatment adverse reactions. Pairwise meta-analysis was conducted for binary and continuous outcomes, while pooled fracture incidence utilized single-arm meta-analysis.

Results: Post-OLT fracture incidence was reported in nine studies (n=591). Total fracture incidence was 6.6% (CI: 3.4% to 12.4%) in bisphosphonate group and 19.1% (CI: 14.3% to 25.1%) in calcium and vitamin D group. Total fractures were significantly lower in patients on bisphosphonate, compared to calcium and vitamin D (n = 591; OR = 0.037; CI: 0.18 to 0.77; p=0.008) Overall fractures were significantly lower in the oral group (n= 263; OR = 0.26; CI: 0.08 to 0.85, p=0.02) but not in the IV group (n = 328; OR = 0.45; CI: 0.16 to 1.26, p=0.129).

Conclusion: Both oral and IV bisphosphonates are effective in reducing fracture incidence post-OLT compared to calcium and vitamin D. Oral formulations may also have an advantage over IV in reducing bone loss and fracture incidence post-OLT.